3D networks of fibrous materials are preferred for cell growth and proliferation as they mimic the extracellular matrix. Moreover, materials with the multi-dimensional fibers, that is, a combination of nano- and microfibers, are preferred as they would benefit from the high surface area offered by nanofibers and structural integrity imparted by the microfibers. This paper presents a unique and facile way of making such fiber-on-fiber composites from bacterial cellulose nanofibers and polystyrene (PS) microfibers. These composites are unique as the PS microfibers are lipophilic, while the cellulose nanofibers are hydrophilic. This not only enables cell attachment but also ensures nutrition supply. Two types of composites were obtained in this work—interpenetrated and layered—by in situ growth of bacterial cellulose into compressed and uncompressed nonwoven PS fabrics, respectively. The layered composite showed two times the cell growth exhibited by the control, while the interpenetrated composite offered a fourfold cell growth, after 24 h. Later (at 48 h), the interpenetrated composites show a decline in cell growth, while the layered composite showed an increase. The role of hydrophilic cellulose fibers in nutrition supply, lipophilic PS in cell attachment, optimal pore size in cell trapping and surface area in enhanced growth is discussed, in addition to the role of the composite morphology (layered or interpenetrated) in cell growth. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.